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Is it resistance or pseudoresistance? According to a new study published in Circulation, aspirin resistance may be a myth, an artifact of the enteric coating of most aspirin tablets. The coating, which is designed to prevent gastrointestinal side effects caused by aspirin, may delay or conceal the effects of the drug, the study suggests, but the antiplatelet effects of the drug will eventually emerge. According to the authors, the study raises new questions about the value of point-of-care tests designed to detect aspirin resistance.

Before and after receiving a single 325 mg dose or either immediate or enteric coated aspirin, 400 healthy volunteers underwent testing to assess the effect of COX-1 on platelets, which is widely considered to be the basis for the cardiovascular effects of aspirin. In this first phase of the study there were no instances of apparent aspirin resistance in the group of 40 subjects who received plain aspirin. By contrast, 108 out of the 360 subjects who received coated aspirin qualified as non-responders when tested at either 4 hours or at 8 hours.

In the second phase of the study the non-responders underwent repeat testing, at which point the number of nonresponders decreased to 42. In the third phase of the study, no patients were found to be aspirin resistant after either a week of aspirin therapy or when aspirin was added ex vivo.

The study authors, led by Garret FitzGerald, said that their study “failed to find a single person who satisfied” the criteria for aspirin resistance. The results, they said, suggest that people who appear to be aspirin resistant instead exhibit “pseudoresistance, due to delayed and reduced drug absorption” due to the drug coating. “These observations question the value of seeking to diagnose aspirin resistance with single point-of-care diagnostic approaches and support the finding of inconsistent platelet inhibition following enteric coated preparations of aspirin.”

In a comment given to the New York Times, Eric Topol disagreed with the study conclusions and pointed out that the study only used healthy volunteers, who are “very different” from people “who actually have heart disease or other chronic illnesses who are taking various medications.”

Sanjay Kaul sent the following comment:

In this elegantly designed study, the authors demonstrate that the prevalence of true aspirin resistance in a healthy cohort is rare and that the variability in aspirin responsiveness is mostly accounted for by variability in bioavailability (drug exposure) of enteric-coated aspirin. One should, however, exercise caution in not extrapolating from this study in healthy volunteers to patients with heart disease or chronic illnesses which might affect how aspirin works in the body. The concept of aspirin resistance rests on a shaky foundation. It is an unclear entity with unclear diagnosis, unclear mechanism, and unclear clinical relevance. It’s prevalence has been overblown, driven to a large extent by marketing considerations, i.e., development of tests to assess aspirin responsiveness, and availability of expensive alternatives to aspirin such as clopidogrel. Most guidelines appropriately do not endorse testing for aspirin resistance.